1.1 Indication

Clobetasol Propionate Topical Spray, 0.05% is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe plaque psoriasis affecting up to 20% body surface area (BSA) in patients 18 years of age or older. The total dosage should not exceed 50 g (59 mL or 2 fl. oz.) per week. Do not use more than 26 sprays per application or 52 sprays per day. Treatment should be limited to 4 consecutive weeks.

Patients should be instructed to use Clobetasol Propionate Topical Spray, 0.05% for the minimum amount of time necessary to achieve the desired results [see Dosage and Administration (2)].

Use in patients under 18 years of age is not recommended because safety has not been established and because numerically high rates of HPA axis suppression were seen with other clobetasol propionate topical formulations.

1.2 Limitations of Use

Clobetasol Propionate Topical Spray, 0.05% should not be used on the face, axillae, or groin. Clobetasol Propionate Topical Spray, 0.05% should not be used if there is atrophy at the treatment site. Clobetasol Propionate Topical Spray, 0.05% should not be used in the treatment of rosacea or perioral dermatitis.

5.1 Effects on the Endocrine System

Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, using the Cosyntropin Stimulation Test, Clobetasol Propionate Topical Spray, 0.05% demonstrated rates of suppression that were comparable after 2 and 4 weeks of twice-daily use (19% and 15 to 20%, respectively), in adult patients with moderate to severe plaque psoriasis (≥ 20% BSA). In these studies, HPA axis suppression was defined as serum cortisol level ≤18 μg/dL 30-min post cosyntropin stimulation [see Clinical Pharmacology (12)].

Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.

An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.

Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.

Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. [see Use in Specific Populations (8.4)]

5.2 Local Adverse Reactions with Topical Corticosteroids

The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria.

5.3 Allergic Contact Dermatitis

Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.

5.4 Concomitant Skin Infections

In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of Clobetasol Propionate Topical Spray, 0.05% should be discontinued until the infection has been adequately controlled.

5.5 Flammable Contents

Clobetasol Propionate Topical Spray, 0.05% is flammable; keep away from heat or flame.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In controlled, clinical trials with Clobetasol Propionate Topical Spray, 0.05%, the most common adverse reaction was burning at the site of application [40% of subjects treated with Clobetasol Propionate Topical Spray, 0.05% and 47% of subjects treated with Spray Vehicle]. Other commonly reported adverse reactions for Clobetasol Propionate Topical Spray, 0.05% and Spray Vehicle, respectively, are noted in Table 1.

Most local adverse reactions were rated as mild to moderate and they are not affected by age, race or gender.

Systemic absorption of topical corticosteroids has produced hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of Clobetasol Propionate Topical Spray, 0.05%.

Skin: Burning, pruritus, erythema, pain, irritation, rash, peeling, urticaria, and contact dermatitis.

8.1 Pregnancy

8.3 Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when Clobetasol Propionate Topical Spray, 0.05% is administered to a nursing woman.

8.4 Pediatric Use

Use in patients under 18 years of age is not recommended, because safety has not been established and because numerically high rates of HPA axis suppression were seen with other clobetasol propionate topical formulations. Safety and effectiveness in pediatric patients treated with Clobetasol Propionate Topical Spray, 0.05% have not been established [see Warnings and Precautions (5.1)].

Because of higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

8.5 Geriatric Use

Clinical studies of Clobetasol Propionate Topical Spray, 0.05% did not include sufficient numbers of patients aged 65 and over to adequately determine whether they respond differently than younger patients. In two randomized, vehicle controlled clinical trials, 21 of the 240 patients (9%) were over the age of 65. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

12.1 Mechanism of Action

Like other topical corticosteroids Clobetasol Propionate Topical Spray, 0.05% has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids in general is unclear. However, corticosteroids are thought to act by induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

12.2 Pharmacodynamics

12.3 Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion.

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and other disease processes in the skin may increase percutaneous absorption.

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through metabolic pathways similar to systemically administered corticosteroids. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Clobetasol propionate was not carcinogenic to rats when topically applied for 2 years at concentrations up to 0.005% which corresponded to doses up to 11 μg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m2/day basis).

Clobetasol propionate at concentrations up to 0.001% did not increase the rate of formation of ultra violet light-induced skin tumors when topically applied to hairless mice 5 days per week for a period of 40 weeks. Clobetasol propionate was negative in the in vitro mammalian chromosomal aberration test and in the in vivo mammalian erythrocyte micronucleus test.

The effect of subcutaneously administered clobetasol propionate on fertility and general reproductive toxicity was studied in rats at doses of 0, 12.5, 25, and 50 μg/kg/day. Males were treated beginning 70 days before mating and females beginning 15 days before mating through day 7 of gestation. A dosage level of less than 12.5 μg/kg/day clobetasol propionate was considered to be the no-observed-effect-level (NOEL) for paternal and maternal general toxicity based on decreased weight gain and for male reproductive toxicity based on increased weights of the seminal vesicles with fluid. The female reproductive NOEL was 12.5 μg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m2/day basis) based on reduction in the numbers of estrous cycles during the pre-cohabitation period and an increase in the number of nonviable embryos at higher doses.

Storage: Keep tightly closed. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do not freeze, refrigerate or store above 30°C. Spray is flammable; avoid heat, flame or smoking when using this product.

17.1 Information for Patients

Patients using topical corticosteroids should receive the following information and instructions:

• This medication is to be used as directed by the physician and should not be used longer than the prescribed time period.
• This medication should not be used for any disorder other than that for which it was prescribed.
• Do not use other corticosteroid-containing products while using Clobetasol Propionate Topical Spray, 0.05% unless directed by your physician.
• The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.
• Patients should wash their hands after applying the medication.
• Patients should report any signs of local or systemic adverse reactions to the physician.
• Patients should inform their physicians that they are using Clobetasol Propionate Topical Spray, 0.05% if surgery is contemplated.
• If you go to another doctor for illness, injury or surgery, tell that doctor you are using Clobetasol Propionate Topical Spray, 0.05%.
• This medication is for external use only. It should not be used on the face, underarms, or groin area. Also avoid contact with the eyes and lips.
• As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.
• Patients should not use more than 50 g (59 mL or 2 fl.oz.) per week of Clobetasol Propionate Topical Spray, 0.05%.
• Do not use more than 26 sprays per application or 52 sprays per day.
• This medication is flammable; avoid heat, flame or smoking when applying this product.

17.2 Instructions to the Pharmacist:

1. Remove the spray pump from the wrapper
2. Remove and discard the cap from the bottle
3. Keeping the bottle vertical, insert the spray pump into the bottle and turn clockwise until well-fastened
4. Dispense the bottle with the spray pump inserted